Disease-Modifying Drugs May Lower Diabetes Risk

A study of RA and psoriasis patients finds certain DMARDs may lower the risk of type 2 diabetes.

| By Jennifer Davis

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There may be an additional bonus for people with rheumatoid arthritis or psoriasis who take certain disease-modifying antirheumatic drugs (DMARDs) to treat the conditions. A study, published in 2011 in the Journal of the American Medical Association, found that several of these drugs – including hydroxychloroquine and TNF-alpha inhibitors – are associated with a reduced risk of developing type 2 diabetes.

“I don’t think we’ve proven [these] drugs are good or bad for diabetes,” says lead researcher Daniel H. Solomon, MD, chief of clinical research in the division of rheumatology at Brigham and Women’s Hospital in Boston. “It may be that people on these drugs have the added benefit of a reduced risk of diabetes, but further studies will help define this issue.”

Type 2 diabetes develops when the body loses its ability to effectively use the insulin it produces. This insulin resistance, as it’s called, results in sugar staying in the bloodstream instead of being stored in cells for energy. It is believed that inflammation plays a role in insulin resistance; people who have systemic inflammatory conditions such as rheumatoid arthritis, or RA, are predisposed to developing insulin resistance.

The retrospective study tracked nearly 14,000 RA and psoriasis patients, with an average follow-up of almost six months, after they started one of four groups of DMARDs:

the biologic TNF-alpha inhibitors etanercept, or Enbrel; adalimumab, or Humira; and infliximab, or Remicade – with or without other DMARDs

methotrexate – with or without other non-biologic DMARDs but without TNF-alpha inhibitors or hydroxychloroquine sulfate

hydroxychloroquine sulfate, or Plaquenil – with or without other non-biologic DMARDs but without TNF-alpha inhibitors or methotrexate

other non-biologic DMARDs, including sulfasalazine, or Azulfidine; leflunomide, or Arava; and cyclosporine or Sandimmune – without TNF-alpha inhibitors, methotrexate or hydroxychloroquine sulfate

During the study period, there were 267 new cases of diabetes among subjects. When researchers sorted through that data, they found that the risk of developing type 2 diabetes was lower among those on TNF-alpha inhibitors and hydroxychloroquine compared with the other categories. There was also a reduced risk among those on methotrexate, but it was not statistically significant. Study subjects treated with other non-biologic DMARDs had the highest rate of newly diagnosed diabetes among the four groups.

“There are at least 10 years of basic science data that suggest that inflammation is related to insulin resistance,” explains Dr. Solomon. “So it may be that drugs that work on those specific aspects of inflammation are particularly good at improving insulin metabolism.”

But Dr. Solomon and others stress that it’s far too early for doctors to change the RA medications they're prescribing for patients to take advantage of this possible benefit.

“Although these findings are exciting and important, especially when considering the problem of cardiovascular disease in patients with rheumatoid arthritis and psoriasis, it’s too early to draw any conclusions for clinical management,” says rheumatologist Tim Bongartz, MD, an assistant professor of medicine at the Mayo Clinic in Rochester, Minn., and the co-author of an editorial accompanying this study. “There’s clearly more work needed to confirm these findings and see how they could be used in a clinical setting.”

Still, although there are no guarantees based on one study, Dr. Bongartz says that, as a clinician, he is hopeful that this finding offers the possibility of one day reducing a patient’s pill burden by addressing inflammatory conditions and diabetes with one medication.

“If you look at a patient with rheumatoid arthritis, our increasing knowledge about all the associated problems with inflammatory disease is also somewhat of a curse. We know about the association with osteoporosis, so they get calcium and vitamin D. We know about a strong association with cardiovascular disease, so we are aggressive with managing risk factors. If you are able to utilize medications which are able to hit two birds with one stone – really reducing the pill burden we put on our patients – I think that would be significant progress and help us to improve compliance,” Dr. Bongartz says.

If other studies confirm these findings, it may become standard practice to assess insulin resistance in patients with inflammatory disease, says Dr. Solomon. But this study alone will not lead to that.

He and his research team are now testing this hypothesis in a National Institutes of Health-funded randomized clinical trial of hydroxychloroquine in RA patients. Until the results of those and other related studies are in, he says patients and providers would do best to focus on lifestyle modifiers, such as exercise and weight loss, that reduce the risk of diabetes.